For a person with lupus, it’s one thing to hear about a breakthrough in the laboratory.

It’s another to get treated with a new drug or procedure that makes life with this chronic autoimmune disease easier to bear. By expediting clinical research in innovative ways, the LRI is finding ways to make this happen.

The institute’s bold approach comes not a moment too soon. For decades, drug developers shied away from testing new lupus therapies because the disease manifests so differently from one person to another, making it difficult to determine whether an approach is effective—let alone safe.

It’s also extremely challenging to collect a large and homogenous sample group of people with lupus. Clinical trials can stretch out over many years before generating meaningful results.

Meanwhile, the need for therapies stays intense, with many patients forced to take powerful medicines with toxic and often debilitating effects.

Finding Solutions

The LRI is forging paths past these barriers that have hampered progress in caring for people with lupus for so long. Its most powerful tactic: backing innovative strategies for identifying, developing, and validating biomarkers (early predictors) of disease activity, damage to organs, and response to therapies.

Biomarkers have proved crucial in studying and treating other complex diseases, such as HIV-AIDS. They hold out the promise of slashing the time it takes to conduct a clinical trial from six years to six months, for example.

In 2004 alone, six of the 13 research projects the LRI funded focus directly on lupus biomarkers. Another five target translational research—moving findings from the lab to the clinic. And in 2002 the LRI launched the Clinical Trials Initiative, a program that encourages scientists to find methodologies that can likewise minimize the time needed to assess a therapy’s effectiveness.

In all, since its inception, the LRI has awarded millions in research grants that have in turn generated biomarker findings with the potential, among other things, to rapidly accelerate the development of new treatments. Grants went to:

• Susan A. Boackle, MD, University of Colorado Health Sciences Center, Denver, CO
  Role of Complement Receptor 2 in Systemic Lupus Erythematosus
• Timothy W. Behrens, MD, University of Minnesota Medical School, Minneapolis, MN
  Serum Protein Biomarkers for Disease Activity in Human S.L.E.
• Robert Clancy, PhD, New York University School of Medicine, New York, NY
  Circulating Endothelial Cells, a Biomarker to Predict Subclinical Atherosclerosis in Patients with S.L.E.
• Mary Crow, MD, Hospital for Special Surgery, New York, NY
  Biomarkers of Disease Flare in S.L.E.
• Anne Davidson, MD, Columbia University, New York, NY
  Biomarkers for Renal Remission in S.L.E.
• Bevra Hahn, MD, University of California at Los Angeles, CA
  Aberrant HDL as Biomarker for Heart Disease in S.L.E.
• Mariana J. Kaplan, MD, University of Michigan, Ann Arbor, MI
  Endothelial Cell Death in Females with S.L.E.; Mechanisms and Associations with Premature Vascular Disease
• Chau-Ching Liu, MD, PhD, University of Pittsburgh School of Medicine, Pittsburgh, PA
  Anti-Lymphocyte Autoantibodies and Lymphocyte-Bound Complement Activation Products: New Allies as SLE Biomarkers
• Elahna Paul, MD, PhD, Massachusetts General Hospital, Boston, MA
  Reaction of Kidney Cells to Autoimmune Attack in Lupus Nephritis
• David Pisetsky, MD, PhD, Duke University Medical Center, Durham, NC
  The Role of HMGB1 in the Pathogenesis of S.L.E.
• Luminita Pricop, MD, Hospital for Special Surgery, New York, NY
  Genetic Mutation of Fc Receptor as Stimulant to Inflammation in S.L.E.
• Chaim Putterman, MD, Albert Einstein College of Medicine, Bronx, New York, NY
  The Human Renal Target for Anti-DNA Antibodies
• Hanno B. Richards, MD, University of Florida, Gainesville, FL
  Prognostic Indicators in Lupus Nephritis
• Robert A. S. Roubey, MD, University of North Carolina at Chapel Hill, NC
  Biomarkers of Blood Clotting in S.L.E. and APS
• Joan Von Feldt, MD, University of Pennsylvania, Philadelphia, PA
  The Role of EBCT in Identification of Premature Atherosclerosis in S.L.E. Patients: Association of Coronary Calcification with Traditional and Novel Cardiovascular Risk Factors
• Edward K. Wakeland, PhD, University of Texas Southwestern Medical Center, Dallas, TX
  Evaluation of Therapeutic Targets for Systemic Autoimmunity
• Martin Weigert, PhD, University of Chicago, Chicago, IL
  Light Chain Editors and Autoimmunity
• Martin Weigert, PhD, University of Chicago, Chicago, IL
  The Regulation and Loss of Regulation of Anti-DNA B cells
• Robert Winchester, MD, Columbia University College of Physicians and Surgeons, New York, NY
  Identification of biomarkers in circulating blood cells that identify events in the molecular pathogenesis of S.L.E. nephritis

Biomarkers Fact Sheet

The goal: identification and validation of early biomarkers for lupus.

Biomarkers defined

The cellular, molecular, or genetic alterations by which a normal or abnormal biologic process can be recognized or monitored are known as biomarkers.

How biomarkers can be used

In many fields, biomarkers are used to predict the risk of contracting a disease or to confirm a diagnosis. In some situations, biomarkers are used to formulate a prognosis, or monitor the response to therapy. For example, high blood pressure is a predictor of increased risk of heart disease. In addition to monitoring response to therapy, biomarkers in lupus may also prove useful to confirm remission and to determine which patients are more likely to relapse.

Surrogate markers explained

If validated at some point, some biomarkers may even become lupus outcomes surrogate markers—laboratory measurement or physical sign that gives an indication of how we are progressing in treating a disease. The marker signals, but does not directly measure, patients' progress in terms of how they feel, how they are functioning or for some diseases, if they will survive. For example, by measuring the level of virus in the blood for patients with AIDS, doctors are able to tell if the medicines are working. In addition, by measuring bone mineral density, the FDA can assess the effectiveness of drugs for treating osteoporosis.

The challenge of finding specific biomarkers for lupus

Many complications have delayed the development of reliable biomarkers. Lupus is unpredictable and manifests itself differently in each person. In addition, many lupus patients may have other diseases, even other autoimmune diseases, which make it difficult to determine whether the lupus or another disease is causing a certain change in the body. Furthermore, many of the studies have not been rigorous enough to provide useful information.

In other fields, this has involved large, multi-center studies to identify potential biomarkers, to validate that the candidate biomarker can be reproducibly measured in many sites, to document that the candidate biomarker actually measures what is intended, and then to correlate changes in the biomarker with variations in some aspect of lupus. Large studies requiring participation of numerous scientists with diverse backgrounds are necessary for this to be successful.

Examples of lupus biomarkers

It is hoped that anti-dsDNA (antibodies that attack the genes inside cells) levels will one day be considered a useful biomarker of therapy progression in treating lupus patients. Other examples include products of the complement system (proteins that function as part of the immune system), and detailed measurement of the status of particular sub-sets of white blood cells known to be involved in lupus activity.